Characterization of Sexual Dimorphism in the Brain

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Project Summary Social interactions are powerfully modulated by internal physiological state and future goals. The goal of our project is a functional and molecular characterization of the mammalian bed nucleus of the stria terminalis (BNST), with a focus on its medial division posteromedial compartment (BNSTmpm). The BNSTmpm is sexually dimorphic across many mammalian species, and it has been implicated in a diversity of social interactions in both sexes and physiological responses. Consistent with these observations, BNSTmpm neurons express the enzyme aromatase that converts testosterone or related androgens into estrogens; aromatase activity is essential for wildtype sexual differentiation of the brain and behavior in both sexes in rodents and many other animals. However, the function of aromatase in different brain regions in adult animals remains poorly characterized. The research goals of the diversity supplement fit within the goals of the parent project, and in particular they are focused on a subset of the specific aims. We have identified a small subset of BNSTmpm neurons that are activated upon mating in females. In aim 1 of the supplement, we will use FosTrap to label these neurons and use fiber photometry to understand the specific components of mating that activate these cells. We will next use chemogenetic actuators to test if these mating-activated BNSTmpm neurons are necessary or sufficient for female reproductive behaviors. In aim 2 of the supplement, we will specifically delete aromatase in BNSTmpm neurons to test its functional contribution to sexually dimorphic social interactions and physiology in both sexes. In summary, the studies proposed for the diversity supplement fit within the overarching goals of the parent project. Health Relatedness: Neurodegenerative and psychiatric conditions often reflect dysfunction of neural circuitry at a gross or microscopic level, and these remain poorly understood and therapeutically intractable. The BNST is a critical node linking amygdalar, hypothalamic, and cortical networks in the regulation of social interactions, response to various stressors, and reward pathways. Our proposed studies will shed light on the connectivity and functions of a subset of BNST neurons in the two sexes, thereby leading to an advance in basic scientific understanding of this region and the neural circuits within which it functions in health, and it may ultimately provide insights into future therapeutic or diagnostic applications for mental illness and common neurodegenerative conditions.